Abstract PS1-08-19: Addressing real-world diagnostic and therapeutic gaps in HER2-low metastatic breast cancer: A quality improvement initiative in community oncology settings

Abstract Background: Accurate interpretation and reporting of HER2 testing results are essential for treatment selection in both HR+/HER2-negative and triple-negative metastatic breast cancer (mBC). The emergence of HER2-low and HER2-ultralow classifications has expanded therapeutic options, particularly with the availability of novel HER2-directed antibody-drug conjugates (ADCs) demonstrating clinical benefit in patients with low HER2 expression. However, consistent and accurate HER2 assessment remains a significant challenge, especially in community settings, and variability in pathology practices may contribute to missed therapeutic opportunities. This quality improvement (QI) initiative sought to address these challenges and advance evidence-based treatment planning for patients with HER2-low mBC in community oncology clinics by promoting sustainable changes in diagnostic and therapeutic practices. Methods: From 11/2024 to 4/2025, 91 healthcare professionals (HCPs) from 7 community oncology clinics completed baseline surveys assessing practice patterns, barriers, and facilitators related to HER2 testing, collaboration with pathologists, and treatment selection for patients with mBC. Clinics then participated in audit and feedback sessions to review site-specific data, identify root causes of practice gaps, and develop action plans. Representatives from each clinic later convened to review progress toward goals, address ongoing challenges, and refine action plans. Follow-up surveys were collected to assess sustained practice change. Results: Key challenges in identifying HER2-low mBC included interpretation of ambiguous or borderline HER2 results (51%), inconsistencies in testing and reporting (24%), and lack of familiarity with the clinical relevance of HER2-low (24%). Pathology reports infrequently included HER2-low (37%) or HER2-ultralow (17%) status. Additionally, 13% of HCPs noted their pathology reports only list IHC/ISH results that must be interpreted by oncology teams. Only 62% of HCPs found HER2 status to be easily accessible in their electronic medical record (EMR). Multidisciplinary tumor boards (MTBs) occurred at least monthly according to 53% of HCPs, yet pathologist participation was limited (55%). While 55% of HCPs were at least moderately comfortable (3/4/5 on 5-point Likert scale) interpreting and applying HER2 testing results to treatment decision-making, only 32% were very likely (5 on 5-point Likert scale) to recommend guideline-directed HER2-directed ADC therapy for a patient with HER2 IHC 1+ or 2+/ISH negative mBC. Top challenges cited regarding treatment selection included staying up to date with the latest approvals and guideline updates for patients with HER2-low disease (37%), and sequencing therapies for patients with other biomarker-directed treatment options (36%). These findings informed action plans to standardize reporting of HER2 results, improve multidisciplinary communication, integrate process improvements to MTBs, and improve HCP education on advances in HER2-low/-ultralow mBC. Follow-up surveys indicated improvements in HER2-low BC identification, communication with pathologists, review of prior pathology reports, and rebiopsy frequency to reassess HER2 status. Conclusions: This study identified gaps in HER2 reporting that hindered accurate identification of HER2-low mBC and selection of HER2-directed ADCs in community oncology practices. Future directions include a national survey of pathologists to identify barriers to consistent HER2-low reporting and to inform standardized workflows and communication strategies across oncology and pathology teams. Supporter: Supported by educational grants from Daiichi Sankyo, Inc. and AstraZeneca Pharmaceuticals. Citation Format: J. Meisel, N. Sidiropoulos, K. Valla, M. S. Nawaz, I. Dewald, S. Dooyema, J. Carter, C. Heggen, M. Kelly. Addressing real-world diagnostic and therapeutic gaps in HER2-low metastatic breast cancer: A quality improvement initiative in community oncology settings [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-08-19.